DESCRIPTION: (Applicant's Abstract) Cocaine remains an important drug of abuse in the United States, and aside from producing profound behavioral effects, cocaine also disrupts neuroendocrine function in many species. Knowledge of the effects of drugs of abuse on neuroendocrine function is of fundamental importance because it provides information on the pathophysiological changes that can occur with drug use. Cocaine stimulates the hypothalamo-pituitary-adrenal (HPA) axis, and disruption of the normal regulation of the HPA axis can affect the maintenance of physiologic homeostasis by altering the metabolism of glucose, proteins and fats. In addition, immune function can be compromised as well as the reaction and adaptation to acute and chronic stress. Recently it has become apparent that exposure to stressors as well as pharmacological manipulation of the HPA axis can affect the responses to and the reinforcing properties of some drugs of abuse. Thus, exposure to stressors and subsequent activation of the HPA axis might play a critical role in determining "vulnerability" to drug self-administration. Although numerous preclinical studies examining the effects of cocaine on neuroendocrine function have been published, little is known about the effects of the self-administration of cocaine on neuroendocrine function. The overall goal of the proposed experiments is to utilize an experimental system where blood can be sampled for hormones in rats during the self-administration of cocaine in order to obtain potentially important information on the relationships between activation of the HPA axis and drug self-administration. The proposed studies will characterize the relationships between self-administered cocaine and activation of the HPA axis by generating dose response and time course data during the acquisition, maintenance, extinction and re-initiation phases of cocaine self-administration. The hypothesis that the active (response contingent) versus passive (response non-contingent) administration of cocaine differentially affects the HPA axis will be tested by comparing subjects that receive cocaine under different response contingencies. The proposed studies also will generate new information on whether prior activation of the HPA axis through pharmacologic and non-pharmacologic means alters the effects of self-administered cocaine on the HPA axis and the reinforcing properties of cocaine. The results of these experiments could provide new and important insights on the relationships between stress and drug seeking behavior.